Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcR? from LIR-1+ NK cells

Nandini Makwana, Bree Foley, S. Lee, Sonia Fernandez, A.B. Irish, P. Price

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimWhile it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcR?, a signaling adaptor molecule, on CD56dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-a and CD107a expression. The most active NK cells were FcR?–LIR-1+NKG2C– and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcR? but express LIR-1.
Original languageEnglish
Pages (from-to)2597-2608
JournalEuropean Journal of Immunology
Volume46
Issue number11
DOIs
Publication statusPublished - 2016

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